Equine infectious anemia virus (EIAV) is unique among lentivirus systems in that infected horses routinely progress from chronic disease characterized by recurring viremias and clinical episodes to a long term inapparent state in which host immune responses maintain a strict control of virus replication and prevent clinical signs of disease. Thus EIAV serves as a novel natural model for the immunologic control of a lentivirus infection, despite the array of persistence and escape mechanisms employed by EIAV. The identification of the specific humoral and cellular immune responses that evolve to overcome aggressive EIAV replication and disease can provide important insights into strategies for the development of immunization procedures for the prevention or treatment of HIV infection and disease in humans. The current competitive renewal application proposes the following specific aims: (1) To extend the analysis of linear and conformational B- and T-cell determinants of the major antigens of EIAV by using an extensive panel of recombinant and synthetic peptide antigens to analyze the targets of humoral and cellular immune responses in inapparently infected ponies; (2) To characterize the evolution of EIAV-specific immune responses as experimentally infected ponies progress from chronic EIA to the inapparent State. Using the panel of antigens and assays defined in the preceding specific aim, this longitudinal study will determine the kinetics of immune responses with respect to the progression of EIAV infection and disease; and (3) To evaluate selected immunogens and vaccination strategies for their ability to elicit protective immune responses against EIAV infection and disease. This specific aim will be a direct testing of the immune correlates indicated in the preceding two specific aims to determine if experimental immunization strategies can elicit immune protection comparable to the immune status achieved in persistent EIAV infections.